1. Field of the Invention
This invention relates to a new anthracycline derivative, 3'-deamino-3'-morpholino-carminomycin, and pharmaceutically acceptable acid addition salts thereof. Also provided by the present invention are new and efficient processes for the preparation of two known anthracycline derivatives, 3'-deamino-3'-morpholino-daunomycin and 3'-deamino-3'-morpholino-adriamycin (including acid addition salts thereof), as well as the above-described carminomycin derivative.
2. The Prior Art
Daunomycin (U.S. Pat. No. 3,616,242) and adriamycin (U.S. Pat. No. 3,590,028) which are obtained from cultured broths of certain strains of Streptomyces have a broad antitumor spectrum against various experimental tumors and are used clinically as potent chemotherapeutic agents. The anthracycline glycoside, carminomycin (U.K. Pat. No. 1,426,637; Cancer Chemotherapy Rep. 58 (2): 255-256, 1974), has also shown activity against a variety of experimental tumors and is being evaluated clinically in the Soviet Union and other countries. While daunomycin and adriamycin and carminomycin are relatively effective as antitumor agents, their effects are by no means ideal, both with respect to spectrum of activity and toxicity problems.
Because of the recognized problems with presently available anthracyclines, extensive research has been carried out to produce new anthracycline derivatives having better antitumor activity and/or reduced toxicity. Illustrative of the newer anthracycline antitumor agents which have been reported are the following:
1. U.S. Pat. No. 3,988,315 discloses aclacinomycin A and B prepared by fermentation of Streptomyces galilaeus.
2. U.S. Pat 4,303,785 discloses inter alia 4'-O-tetrahydropyranyl daunomycin and adriamycin.
3. U.S. Pat No. 4,177,264 discloses N-benzyl and N,N-dibenzyl derivatives of adriamycin and daunomycin.
4. U.S. Pat No. 4,202,967 discloses N,N-pentamethylene derivatives of daunomycin and adriamycin.
5. U.S. Pat. No. 4,301,277 discloses 3'-deamino-3'-morpholino-adriamycin and 3'-deamino-3'-morpholino-daunomycin by reductive alkylation of adriamycin or daunomycin.